Impact of Synthetic Biology on Secondary Metabolite Biosynthesis
Natural products are structurally diverse bioactive secondary metabolites produced by a wide range of microorganisms, fungi, and plants. Recent advances in (meta)genome sequencing have led to an explosive identification of putative secondary metabolic pathways. The number of known natural products is now dwarfed by the sum of putative pathways encoded in the genomes of highly characterized organisms, uncultivated microbes, and even those from completely unknown sources. The normal route of secondary metabolite discovery from bioactivity, to structure elucidation, to biosynthetic pathway—the bedrock of the natural products field—now has to be often approached in a reversed workflow. New methods to quickly identify structural novelty and predict bioactivity need to be developed, as well as efficient ways to produce natural products and manipulate their pathways in heterologous hosts. The nascent field of synthetic biology has the potential to effectively tackle problems faced by this generation's natural products researchers. Born out of systems biology and genetic engineering, synthetic biology applications attempt to decouple unknown metabolic and regulatory constraints from native pathways to rationally and predictably control the biosynthesis of a metabolite of interest. This chapter highlights the recent progress and influence synthetic biology has had on natural product discovery, production, and diversification. Looking to the future, synthetic biology principles will inevitably be needed to unlock Nature's true potential to inspire the next generation of therapeutics and biomaterials.